Activation of professional antigen presenting cells by acharan sulfate isolated from giant african snail,achatina fulica

Acharan sulfate isolated from the giant African snail, Achatina fulica, has been reported to have antitumor activity in vivo. In an effort to determine the mechanisms of its antitumor activity, we examined the effects of acharan sulfate on professional antigen presenting cells (APCs). Acharan sulfate increased the phagocytic activity, the production of cytokines such as TNF-alpha and IL-1beta, and the release of nitric oxide on a macrophage cell line, Raw 264.7 cells. In addition, acharan sulfate induced phenotypic and functional maturation of immature dendritic cells (DCs). Immature DCs cultured with acharan sulfate expressed higher levels of class II MHC molecules and major co-stimulatory molecules such as B7-1, B7-2, and CD40. Functional maturation of immature DCs cultured in the presence of acharan sulfate was confirmed by the increased allostimulatory capacity and IL-12 production. These results suggest that the antitumor activity of acharan sulfate is partly due to the activation of professional antigen presenting cells.     

Anti-angiogenic and anti-tumor activities of isoflavonoids from the rhizomes of Belamcanda chinensis

The present study was carried out to clarify whether tectorigenin and tectoridin isolated from the rhizomes of Belamcanda chinensis (Iridaceae) inhibit angiogenesis by the experimental methods in vitro and in vivo. Tectorigenin and tectoridin decreased angiogenesis of both chick embryos in the chorioallantoic membrane assay and basic fibroblast growth factor-induced vessel formation in the mouse Matrigel plug assay. Both compounds also reduced the proliferation of calf pulmonary arterial endothelial (CPAE) cells and found to possess relatively weak gelatinase/collagenase inhibitory activity in vitro. Tectorigenin exhibited a much stronger anti-proliferative activity than its glycoside, tectoridin and was almost equipotent to that of genistein, a reference drug. Tectorigenin, when administered subcutaneously at the dose of 30 mg/kg for 20 days to mice implanted with murine Lewis lung carcinoma (LLC), caused a significant inhibition of tumor volume by 30.8 %. Tectorigenin and tectoridin, when treated i. p. at the same dosage for 10 days to ICR mice bearing sarcoma 180, caused a significant suppression in tumor weight by 44.2 and 24.8 %, respectively.     

Anti-angiogenic and anti-tumor activities of 2'-hydroxy-4'-methoxychalcone

In the present study, we evaluated the in vitro and in vivo anti-angiogenic and anti-tumor activities of 2'-hydroxy-4'-methoxychalcone (HMC). HMC decreased angiogenesis in both chick embryos in the chorioallantoic membrane assay and basic fibroblast growth factor (bFGF)-induced vessel formation in the mouse Matrigel plug assay. This compound also reduced the proliferation of calf pulmonary arterial endothelial cells and was found to possess relatively weak gelatinase/collagenase inhibitory activity in vitro. HMC, when administered subcutaneously at the dose of 30 mg/kg for 20 d to mice implanted with murine Lewis lung carcinoma, caused a significant inhibition of tumor volume by 27.2%. Intraperitoneal (i.p.) treatment at the same dosage for 10 d to ICR mice bearing sarcoma 180 caused a significant suppression in tumor weight by 33.7%. Taken together, out data demonstrate that the anti-angiogenic activities of HMC might be due to anti-proliferative activity under inhibition of the induction of COX-2 enzyme. Furthermore, the results suggest that the potent anti-angiogenic activity of HMC seems to be the possible mechanism of action in these animal models of solid tumors.     

Inhibition of in vivo angiogenesis by N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine

N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine (5-S-GAD), an antibacterial substance isolated from the flesh fly, inhibits human tumor growth in the nude mice model; however, the mechanism of its action is unclear. The in vivo antitumor effect includes the inhibition of tumor cell proliferation and suppression of angiogenesis. Angiogenesis is essential for tumor growth in vivo. In this study, we examined whether 5-S-GAD inhibits tumor cell-induced angiogenesis by performing the mouse dorsal air sac assay. We found that intraperitoneal administration of 5-S-GAD inhibited the angiogenesis induced by S180 mouse sarcoma cells. Furthermore, 5-S-GAD also inhibited vascular endothelial growth factor-induced angiogenesis in the Matrigel plug assay and embryonic angiogenesis in the chick embryo chorioallantoic membrane assay. However, 5-S-GAD did not show any effect on the proliferation, migration, and tube formation of vascular endothelial cells. These results provide the first evidence that a bioactive substance derived from the flesh fly has antiangiogenic activity in vivo, although the mechanisms involved could not be explained.     

人尿提取物抗肿瘤活性研究

目的　研究人尿提取物的抗肿瘤活性。方法　从人尿中提取到一种小肽混合物UAP(uricantitumorpeptides) ,用细胞计数法和MTT法测定UAP对 3种人肿瘤细胞SMMC772 1,MKN4 5和U937生长的抑制作用 ,并对其进行体内实验和急性毒性实验。结果　人尿中的提取物UAP对体外培养的SMMC772 1,MKN4 5和U937细胞具有抑制作用 ,但对人正常白细胞HNL(humannormalleucocyte)无明显抑制作用 ,体内实验表明UAP对小鼠HAC肝癌 ,小鼠LEWIS肺癌和小鼠S180 肉瘤瘤体生长有明显抑制作用。急性毒性试验显示其的毒性作用很低 ,LD50 =2 137 13mg·kg-1。结论　人尿中此种小肽提取物在体外体内实验中均有明显的抑瘤作用     

A potential role of bradykinin in angiogenesis and growth of S-180 mouse tumors

Angiogenesis is an important event in tumor growth. We evaluated the contribution of endogenous bradykinin to tumor-associated angiogenesis and tumor growth using pharmacological approaches in mice bearing sarcoma 180 cells. The weight of implanted tumors increased in parallel with increased hemoglobin contents (a parameter to evaluate angiogenesis) over a 20-day experimental period. Daily administration of bradykinin B2-receptor antagonists, Hoe140 (0.1 and 1 mg/kg per day, local injection) or FR173657 (30 mg/kg per day, p.o.), significantly suppressed the increment in angiogenesis and tumor weight, but a B1-receptor antagonist, desArg10-Hoe140 (1 mg/kgperday), did not. Administration of a plasma kallikrein inhibitor, soybean trypsin inhibitor (3 mg/site per day), significantly suppressed angiogenesis and tumor growth. In contrast, bradykinin-degrading enzyme inhibitors, captopril and phosphoramidon (500 microg/site per day), enhanced angiogenesis and increased tumor weight. Our results suggest that bradykinin, produced by plasma kallikrein or plasma kallikrein-like enzymes, promote tumor-associated angiogenesis and tumor growth in vivo.     

聚酯型儿茶素的抗肿瘤及免疫调节作用

目的：研究聚酯型儿茶素（ＴＳ）对小鼠移植瘤的抑制作用及对荷瘤小鼠免疫功能的影响。方法：应用小鼠艾氏腹水癌实体型、小鼠Ｓ１８０肉瘤和肝癌Ｈ２２３种模型进行了ＴＳ的抗肿瘤作用研究;应用小鼠迟发型超敏反应模型、小鼠碳粒廓清试验及脾淋巴细胞增殖试验研究了 ＴＳ对荷Ｓ１８０小鼠免疫功能的影响。结果：４００、２００、５０ｍｇ／ｋｇ ＴＳ对小鼠艾氏腹水癌实体型瘤生长有明显抑制作用;常规灌胃给药对小鼠Ｓ１８０和肝癌Ｈ２２的生长无明显抑制作用,但预防给药则对小鼠Ｓ１８０和肝癌Ｈ２２的生长有明显抑制作用,各组抑瘤率均大于 ３０％。５０、１００、２００ｍｇ／ｋｇ ＴＳ可使荷瘤小鼠降低的迟发性超敏反应恢复正常;亦可使荷瘤小鼠碳粒廓清指数 Ｋ和吞噬指数α值显著提高;还可明显增强荷瘤小鼠脾Ｔ淋巴细胞增殖反应。结论：ＴＳ对小鼠移植瘤有明显抑制作用,同时可增强荷瘤小鼠降低的免疫功能。     

A novel human tumor necrosis factor alpha mutant showed potent antitumor activity and reduced toxicity in vivo.

AIM: To study the antitumor activity and systemic toxicity of human tumor necrosis factor alpha (hTNFalpha) mutant M2 (R2K-N30S-R32W-L157F-hTNFalpha). METHODS: Mouse sarcoma S180 tumors and hepatoma HAC tumors were implanted into mice, and human urocyst carcinoma CP-3 tumors were implanted into nude mice. The xenografted mice were injected with wild-type hTNFalpha and its mutant M2 at different doses. After 7 d (mice) or 10 d (nude mice) of injection, the tumor weight was measured to calculate the inhibition rate of hTNFalpha and M2. Systemic toxicity experiments were done on Rhesus monkeys by injecting them with wild-type hTNFalpha and mutant M2 respectively for 10 consecutive d. Observations were made on the monkeys both before and after the injection. RESULTS: For mice implanted with sarcoma S180 and hepatoma HAC tumors, the inhibition rate of M2 was similar to that of wild-type hTNFalpha at the dose of 0.025 mg/kg, while for nude mice implanted with human urocyst carcinoma CP-3, the inhibition rate of M2 (45.5 %) was much higher than that of wild-type hTNFalpha (15.5 %). When the dose came to 0.25 and 2.5 mg/kg respectively, however, the inhibition rate of M2 greatly increased (the highest was 75.9 %). The tests of systemic toxicity of hTNFalpha and its mutant M2 in monkeys proved that M2 presented lower toxicity than wild-type hTNFalpha did. CONCLUSION: hTNFalpha mutant M2 not only presented higher antitumor activity than wild-type hTNFalpha did on mouse tumor (S180 and HAC)- and human tumor (CP-3)-implanted mice, but also showed lower systemic toxicity in the Rhesus monkey.     

中药CHH复方对小鼠S180肉瘤的抑制作用

目的:探讨中药CHH复方对S180肉瘤荷瘤小鼠的抑瘤作用,为实验研究提供数据参考.方法:以环磷酰胺作为对照组,分析5 mg·kg-1,10 mg·kg-1,20 mg·kg-1剂量的中药CHH复方皮下注射,观察对小鼠S180肉瘤的抑瘤率.结果:5 mg·kg-1剂量的抑瘤率27.4%、10 mg·kg-1剂量的抑瘤率41.6%、20 mg·kg-1剂量的抑瘤率66.0%.结论:试验结果提示CHH复方对小鼠肉瘤S180有明显的抑制作用.     

软骨抗肿瘤制剂的制备及肿瘤实验治疗

小牛软骨经盐酸胍抽提、丙酮分级沉淀及膜超滤等步骤获得了软骨抗肿瘤制剂（Carti-lage Antitumor Preparation, CATP）。利用~3H-TdR参入、测定肿瘤干细胞及细胞死亡率等方法研究了CATP对肿瘤细胞及血管内皮细胞的抑制效应,并对小鼠移植性肿瘤进行了抗肿瘤作用的研究。结果表明:（1）合适浓度的CATP可显著地抑制肿瘤细胞和血管内皮细胞的生长,而不抑制正常细胞;（2）CATP对荷瘤小鼠肿瘤具有明显的抑制作用,抑瘤率为50％～60％。给药组小鼠胸腺重量明显增加,提示CATP可能具有免疫调节作用。实验结果为CATP的临床应用提供了依据。     

丹酚酸A抑制核苷转运并增强化疗药物的抗肿瘤作用丹酚酸A抑制核苷转运并增强化疗药物的抗肿瘤作用

目的观察丹酚酸A(SAA)的抑制核苷转运活性及其抗肿瘤作用。方法用3H-TdR和3H-UR转运测定法,克隆生成测定法以及小鼠移植性肉瘤180模型。结果SAA抑制艾氏腹水癌细胞的胸苷和尿苷的转运,其IC₅₀分别为18.1和17.1 μmol·L^-1。SAA能明显增强5-FU、丝裂霉素C、MTX对KB细胞、肝癌BEL-7402细胞的细胞毒性。体内试验,SAA 200 mg·kg^-1和5-FU 10 mg·kg^-1单独使用的抑瘤率分别为41%和27%;SAA和5-FU联合使用的抑瘤率为63%(CDI=0.86)。结论SAA有抑制肿瘤细胞核苷转运的活性,可增强5-氟尿嘧啶等药物的抗肿瘤作用,有可能用于肿瘤联合化疗。     

白桦三萜类物质抗黑色素瘤B16、S180肉瘤作用及其机制的实验研究

目的　研究白桦三萜类物质 (triterpenesofbetulaplatyphyllasuk .TBP)抗黑色素瘤B16、S180肉瘤及其诱导细胞调亡作用和对细胞周期的影响。方法　建立小鼠体内荷黑色素瘤B16和腹水型S180肉瘤模型 ,测定TBP的抑瘤率和生命延长率。用形态学检测方法 (Giemsa染色法 )和流式细胞光度术检测TBP诱导的细胞调亡和对细胞周期的影响。结果　TBP具有明显的抗肿瘤作用 ,1 2 g·kg-1TBP对黑色素瘤B16的抑瘤率为 5 1 40 % ,对荷S180肉瘤小鼠生命延长率为 41 0 4%。可诱导B16和S180肿瘤发生细胞调亡 ,G0 /G1期细胞比例增加 ,S期细胞比例下降。结论　TBP可明显抑制黑色素瘤B16和S180肉瘤生长 ,其机制与诱导细胞调亡和阻断细胞生长于G0 /G1期有关。     

苦碟子注射液的抗肿瘤作用

目的探讨苦碟子注射液(Kudiezi injection,KDI)抗肿瘤作用。方法体内实验分别采用小鼠肝癌H22、肉瘤S180和Lewis肺癌荷瘤小鼠模型,造模次日小鼠连续7 d给予苦碟子注射液,每天1次。剂量分别为5、10、20g.kg-1。第8天记录每组每只小鼠体质量和瘤质量,计算每组平均体质量和抑瘤率;体外实验采用四甲基偶氮唑盐(MTT)法测人宫颈癌Hela细胞或肝癌HepG-2细胞增殖抑制率;升白实验采用肝癌H22荷瘤小鼠模型,造模次日小鼠连续7 d给予苦碟子注射液,每天1次。剂量分别为5、10、20g.kg-1。第8天记录每组每只小鼠外周血中白细胞数量。结果苦碟子注射液(5、10、20g.kg-1)对3种荷瘤小鼠肿瘤增长有非常显著的抑制作用(P<0.05,P<0.01,P<0.001),同时显著升高肝癌H22小鼠外周血白细胞数量(P<0.05);在体外,苦碟子注射液(12.5~200g.L-1)对人宫颈癌Hela细胞或肝癌HepG-2细胞增殖有非常显著的抑制作用。结论苦碟子注射液体内体外均有抗肿瘤活性,在体内抑瘤的同时能显著升高肝癌H22小鼠外周血白细胞数量。     

双氢青蒿素纳米结构脂质载体在荷S180瘤小鼠体内的抗肿瘤活性及生物分布研究(英文)

近年来脂质纳米粒由于其优越的特征备受青睐。本文通过腹腔注射评价了双氢青蒿素纳米结构脂质载体在荷S180瘤小鼠体内的抗肿瘤作用, 以及在荷S180昆明鼠内的生物分布研究。结果表明双氢青蒿素纳米结构脂质载体显著抑制了肿瘤的增长, 通过腹腔给药在20, 40和80mg/kg时肿瘤抑制率分别为71.24%, 79.20%和85.74%, 在荷S180小鼠体内静脉注射双氢青蒿素纳米结构脂质载体后, 药物的生物分布表明双氢青蒿素纳米结构脂质载体与双氢青蒿素溶液相比, 双氢青蒿素纳米结构脂质载体显示了明显不同的生物分布。因此, 本文实验结果确实证明了双氢青蒿素纳米结构脂质载体与双氢青蒿素普通混悬液相比, 在相同剂量下双氢青蒿素纳米结构脂质载体显示出更优越的抗肿瘤作用和剂量依赖性。     

磷酸肌酸对小鼠移植性S180肉瘤血管生成的作用及机制研究

目的 探讨磷酸肌酸(creatine phosphate,Cp)对小鼠移植性S180肉瘤血管生成的作用及其相关机制.方法 建立昆明小鼠S180肉瘤模型,60只小鼠随机分为4组:0.9%氯化钠溶液对照组(对照组)、Cp低剂量组(200 mg/kg)、Cp中剂量组(400 mg/kg)、Cp高剂量组(800 mg/kg),观察4组小鼠移植瘤重量;流式细胞术测定基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)及金属蛋白酶组织抑制因子-2(tissue inhibitors of metalloproteinases,TIMP-2)蛋白的表达;免疫组化检测肿瘤组织微血管密度(microvasvular density,MVD);RT-PCR检测移植瘤组织中血管内皮生长因子(vascular endothlial growth factor,VEGF)及碱性成纤维细胞生长因子(base fibroblast growth,bFGF)mR-NA的表达水平.结果 对照组、Cp低剂量组和中剂量组移植瘤重量、VEGF、bFGFmRNA、MMP-2、TIMP-2水平比较,差异均无统计学意义(P>0.05);Cp高剂量组与对照组、Cp低、中剂量组比较,小鼠移植性肉瘤质量明显减小,MVD数显著减少,VEGF、bFGFmRNA和MMP-2蛋白表达明显减少,TIMP-2蛋白表达明显增加,差异均有统计学意义(P<0.01).结论 Cp低、中剂量对肿瘤血管生成无明显影响;Cp高剂量对肿瘤血管生成具有明显的抑制作用,其机制可能与通过下调MMP-2、VEGF和bFGF、上调TIMP-2的表达水平有关.     

The anticancer activities of wogonin in murine sarcoma S180 both in vitro and in vivo

The anticancer effects of wogonin on murine sarcoma S180 both in vitro and in vivo were investigated, and its pro-apoptotic molecular mechanism was further studied. Wogonin treatment resulted in significant inhibition of S180 cells in a concentration-dependent manner detected by MTT assay. The IC(50) value for 48 h was (7.37+/-1.53)x10(-5) M. Typical morphological changes and apoptosis bleb phenomenon in S180 cells exposed to wogonin were distinctly observed by the inverted light microscope and the fluorescence microscope, respectively. According to protocols of transplanted tumor research,(1)) mice were transplanted with tumor cells S180. The weight of tumor and the peripheral leucocyte count were observed after the treatment of wogonin. The significant suppression of tumor growth was observed, and the peripheral leucocyte count of S180-bearing mice remained no significant changes compared with control group. After the treatment of 40 mg/kg wogonin, the inhibitory rate of tumor weight was 53.01%. Additional DNA fragmentation assay showed that wogonin induced apoptosis on murine sarcoma S180 tissue. RT-PCR results indicated that the increasing mRNA levels of bax and p53 and the decreasing mRNA level of bcl-2 were induced by wogonin. Western-blot assay showed that the increasing protein level of bax and the decreasing protein level of bcl-2 were induced by wogonin. Collectively, wogonin could induce apoptosis in murine sarcoma S180 thereby inhibiting the tumor growth both in vitro and in vivo. The pro-apoptotic effects might be related to the improvement of mRNA level of p53, the improvement of mRNA and protein levels of bax, and the reduction of mRNA and protein levels of bcl-2.     

SEA体内杀伤S180肉瘤效果及其细胞因子的测定

目的:研究SEA抗肿瘤的效果及其对细胞因子干扰素(IFN)-γ的影响,探讨其作用机制。方法:采用S180细胞建立小鼠肉瘤模型40只进行体内抑瘤实验,随机分成4组,包括SEA高剂量组(n=10)、SEA中剂量组(n=10)、SEA低剂量组(n=10)和对照组(n=10),前3组分别注射0.5、0.25、0.05mg/kg的SEA,对照组注射生理盐水,接种第5天起测量各组小鼠肿瘤体积,绘制肿瘤生长曲线并计算抑瘤率。治疗结束后取小鼠血清并测定IFN-γ的含量。结果:SEA高、中和低剂量组抑瘤率分别为(44.00±3.21)%、(3.92±2.12)%和(2.33±1.95)%,SEA高剂量组脾脏指数和IFN-γ的含量明显增加,与对照组比较差异均有统计学意义(P<0.01),但肿瘤质量却明显减小。结论:SEA通过激活T细胞,分泌细胞因子IFN-γ抑制小鼠体内S180肉瘤生长。     

硫酸壳聚糖体内抗肿瘤作用的实验研究

目的：研究硫酸壳聚糖的体内抗肿瘤作用。方法：用高、低（200、100mg/kg）两个剂量的硫酸壳聚糖分别腹腔注射治疗肉瘤180（S180）小鼠和艾氏腹水癌（EAC）小鼠10d,然后测定其抑瘤率、重要器官的内脏指数和生命延长率,同时设生理盐水组（空白对照组）和氟尿嘧啶组（阳性对照组）进行比较。结果：硫酸壳聚糖高、低剂量组和氟尿嘧啶组的抑瘤率分别为38.67%、30.19%和43.27%,3组的生命延长率分别为65.38%、69.23%和54.93%。和生理盐水组、氟尿嘧啶组相比,硫酸壳聚糖高、低剂量组的S180小鼠的胸腺指数均有明显增加（P〈0.05）。结论：硫酸壳聚糖能有效抑制S180小鼠肿瘤的生长和延长EAC小鼠的生存时间,其作用机制可能与其提高机体的免疫力有关。     

多肽ND100的抗肿瘤活性研究

目的　研究多肽ND100的抗肿瘤活性。方法　用液相法人工合成了抗肿瘤八肽ND100,分子量为 846 9。测定了ND100对 3种小鼠移植性肿瘤的抑制作用,并研究了ND100对小鼠红细胞和白细胞数量的影响。结果　体内抑瘤试验表明,ND100对小鼠H22肝癌、小鼠Lewis肺癌和小鼠S180肉瘤的生长均有明显抑制作用,有效剂量为 2 5mg·kg-1,当使用高剂量时(15mg·kg-1 )时,对 3种小鼠移植性肿瘤的抑制率达 0 70以上,且具有剂效关系。ND100对小鼠红细胞和白细胞的数量均无影响。结论　ND100具有明显的体内抗肿瘤活性。     

Biological activity of the potent uridine phosphorylase inhibitor 5-ethyl-2,2'-anhydrouridine

5-Ethyl-2,2'-anhydrouridine (ANEUR) proved to be a potent inhibitor of uridine phosphorylase isolated from sarcoma 180 cells with an apparent Ki (Ki(app) value of 99 nM. Coadministration of ANEUR with 5-fluorouridine (FUR) resulted in increased toxicity of FUR. The LD50 value of FUR alone was 9 mg/kg (when administered for 5 consecutive days) while the LD50 was 3 mg/kg when FUR was administered together with ANEUR in vivo. There was no significant difference in mean tumor weight on day 10 between control animals and animals treated with FUR (5 mg/kg/day for 3 days) or ANEUR (280 mg/kg/day for 3 days). When FUR was coadministered with ANEUR, mean tumor weight was 91% less than that of the untreated controls, showing that ANEUR, the potent URPase inhibitor, increases the antitumor effect of FUR.